MEG/MRS dose-response study of STX209 in autism spectrum disorder

Timothy Roberts and his colleagues at the Children’s Hospital of Philadelphia are studying the responsiveness of neural oscillatory measures to acute administration of STX209 (arbaclofen), a GABA-B agonist and a candidate therapeutic for autism spectrum disorder (ASD). Previous electrophysiological magnetoencephalographic (MEG) studies have pointed to auditory encoding abnormalities (specifically, delays)1,2 as well as abnormalities in the oscillatory behavior of auditory cortex neurons (especially in the gamma band: 30-50 Hz)3 in individuals with ASD. Preliminary data suggest that a GABA-B agonist may normalize activity in auditory cortex neural circuits in ASD.

In the current study, Roberts and his colleagues plan to examine the acute effects of STX209 on auditory brain activity in individuals with ASD. Three different doses of STX209 (5, 15 and 25 mg), as well as placebo, will be acutely administered as part of a 4-week randomized, crossover trial. A primary goal is to assess the responsiveness (sensitivity to change) of MEG measures to acute administration of STX209 by examining MEG brain measures before, during and after administration of STX209.

The researchers also aim to establish whether such electrophysiological measures are associated with GABA and glutamate levels using MEGA-PRESS spectrally edited magnetic resonance spectroscopy (MRS). This technique has previously been used to demonstrate a relationship between GABA concentration and gamma oscillatory activity in the motor cortex4.

Results from this study are expected to demonstrate the utility of MEG and MRS for assessing the acute effects of STX209 on brain activity, potentially providing a physiologically specific basis for identifying those individuals with ASD most likely to benefit from STX209 treatment (i.e., targeted treatment).